1. Field of the Invention
The use of attenuated or killed pathogens has become a classical technique in vaccination to protect a mammalian host from a pathogen. However, the use of intact organisms has many concerns. It is not sufficient that there be a high rate of kill of the viable organism. Unless one can be assured that there is complete mortality or attenuation, the vaccine becomes the infective agent. Furthermore, where the genome of the organism is retained, there is the further concern that potential complementation can result in a genome which will be capable of replication and become infectious.
Besides the safety concerns, there is also the question of whether the attenuated or killed pathogen will serve as an effective immunogen. Where the lifetime of the modified pathogen in the host is unreasonably short, it may not provide a sufficient period of exposure to develop a strong immunogenic response. Also, the method of attenuating or killing the pathogen may result in conformational modifications of the pathogen. The immunogenic response may therefore be to determinants other than the wild type pathogen.
Finally, there is the concern that the modifying agent, where a chemical reagent is used, must not be detrimental to the host on administration to the host. Therefore, any agent which is used must either be removed prior to administration to the host or alternatively should have little if any detrimental effect on the host.
In view of the numerous constraints on preparing attenuated or killed vaccines, only a few pathogens have been modified and shown to be effective vaccines.
2. Description of the Prior Art
Kutinova et al., Neoplasma (1972) 19:5 describes the inactivation of papovavirus. SV40 by cis-dichlorodiammine platinum (II). Roberts and Thomson, Progress in Nucleic Research and Molecular Biology (1979) 22:71 describe the mechanism of action of antitumor platinum compounds. See also the references cited therein.